Peripheral Retina Changes Could Signal Early Alzheimer's, Research Finds

What if Alzheimer's disease could be detected during a routine eye exam, years before memory loss begins? A new study suggests that early warning signs of the disease may be hiding in the far edges of the retina, not the center typically examined in standard vision tests. The research, led by scientists at Houston Methodist Hospital, was published in the Journal of Alzheimer's Disease.

Alzheimer’s disease (AD) is marked by the buildup of amyloid proteins in the brain, leading to progressive neurodegeneration. Previous studies have shown that amyloid accumulation in the retina mirrors similar deposits in the brain, suggesting the eye may reflect early disease processes. However, most clinical exams focus on the central retina, which is responsible for sharp vision. This new study shifts attention to the peripheral retina—the outer region of the eye.

Using mouse models of early-stage Alzheimer’s, researchers examined how Müller glia—specialized retinal support cells—respond during the earliest phases of disease development. They compared changes between central and peripheral retinal regions. The team found that the peripheral retina, which contains a higher density of glial cells, showed significant structural and cellular alterations before classic neurological symptoms appeared.

A key finding involved Aquaporin-4, a protein that helps clear metabolic waste—including amyloid—from the central nervous system. In early disease stages, Aquaporin-4 levels increased, particularly in the peripheral retina. This was accompanied by enlarged and more numerous glial cells, indicating cellular stress and an intensified effort to maintain tissue balance before widespread brain damage occurs.

Researchers interpret these changes as evidence that the body’s “waste-clearing” system is working harder in the earliest stages of Alzheimer’s. Because these retinal alterations appear before significant cognitive decline, they may offer a valuable window for early detection.

While the findings are based on animal models and require validation in humans, the study suggests that advanced retinal imaging focused on the periphery could one day support earlier diagnosis and monitoring of Alzheimer’s—potentially opening the door to earlier intervention and improved outcomes.

REFERENCE: Das, G., Raghunathan, R., Wang, L., Wan, Z., Vasquez, M., Zhao, H., & Wong, S. T. (2026). Retinal Müller glia alterations and their impact on ocular glymphatic clearance in an Alzheimer’s disease mouse model. Journal of Alzheimer’s Disease. https://doi.org/10.1177/13872877261418165